An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury

Area of Science:

• Nephrology
• Cell Biology
• Pathology

Background:

• Necrosis is the primary cell death mechanism in acute kidney injury (AKI).
• Muddy brown casts in urine sedimentation are diagnostic indicators of AKI, historically termed acute tubular necrosis.
• The molecular mechanisms driving necrotic morphology in AKI are not fully understood.

Purpose of the Study:

• To review candidate molecular pathways involved in regulated necrosis in AKI.
• To summarize emerging evidence on the roles of specific necrosis types, including necroptosis, ferroptosis, and pyroptosis.
• To discuss potential therapeutic targets and inhibitors for regulated necrosis pathways in AKI treatment.

Main Methods:

• Literature review of regulated cell death pathways in AKI.
• Analysis of evidence for necroptosis, ferroptosis, mitochondrial permeability transition-mediated regulated necrosis, parthanatos, and pyroptosis.
• Discussion of available inhibitors and potential clinical trial development.

Main Results:

• Several regulated necrosis pathways contribute to AKI pathogenesis.
• Specific pathways like necroptosis and ferroptosis are highlighted as significant.
• Inhibitors for these pathways exist and show therapeutic potential.

Conclusions:

• Understanding regulated necrosis pathways is crucial for AKI treatment.
• Targeting these pathways with specific inhibitors presents a promising therapeutic avenue.
• Inhibitors of regulated necrosis could be vital in preventing the global burden of AKI.